The literature describes a number of methods for obtaining monovalent polyfunctional bioconjugated complexes (Lemieux et al. Trends in Biotechnology, 1998, 16, 506-513). These complexes evoke a relatively weak biological response, however. Multivalent systems were then prepared (Tam et al., Biomedical Peptides, Proteins & Nucleic Acids, 1995, 1, 123-132). Studies demonstrated that polyvalent complexes were, in general, much better biological tools than monovalent bioconjugated complexes (Grubbs, R. H. et al., J. Am. Chem. Soc., 2001, 123, 1275-1279).
The significance of such bioconjugated complexes is that they combine the properties characteristic of at least two different classes of molecules. One of the difficulties that arises, however, is the potential interaction that the various molecules of a bioconjugate can exhibit. That interaction can modify the properties resulting from bioconjugation. One solution to that problem is to spatially separate the bioconjugation points, which has led to the development of addressable molecular templates or frameworks. L. Scheibler, P. Dumy et al., Tetrahedron, 1998, 54, 3725-3734, disclose the synthesis and characterization of molecular frameworks functionalized with coordination groups and alkane chains.
Attaching the molecules of interest to the framework presents another difficulty. L. Scheibler, P. Dumy et al., Angew. Chem. Int. Ed., 1999, 38, 696-699, disclose a framework that has been chemoselectively functionalized on one face by means of an oxime bond.
The existing art does not, however, teach how to synthesize a framework functionalized on both faces, at least one of the functionalizations being chemoselective, and each face carrying molecules of therapeutic or diagnostic or labeling interest.
It would therefore be advantageous to provide a method for preparing a homodetic cyclopeptide grafted on both of its faces.